These studies will continue to investigate the hypothesis that the accumulation of false neurochemical transmitters (FNT) of the peripheral and central nervous systems may be involved in the symptomatology of hepatic failure. Over the past 2 years the accumulation of octopamine, a known FNT, has been documented in acute hepatic encephalopathy associated with a marked depletion in brain norepinephrine in acute experimental hepatic coma. Therapy efficacious in hepatic coma in man decreases the accumulation of FNT in the brain of rats with chronic liver disease and results in increased brain norepinephrine. Increased amounts of blood and urine octopamine are present in patients with hepatic encephalopathy. In the following grant proposal the mechanisms of accumulation of octopamine and depletion of norepinephrine will be studied using measurements of synthesis and turnover of catecholamines and FNT from labeled precursors, using column chromatography, fluorometry and especially gas liquid chromatography. Using a non-human primate model of chronic liver disease with an indwelling CSF ventricular tap we hope to gain access to the brain metabolism during episodes of hepatic coma and changes in such metabolism during therapy. Several amines have been recovered from patients which appear to be specifically associated with hepatic coma. Using gas liquid chromatography and mass spectrometry an attempt will be made to definitively identify these amines. The ultimate purpose of these studies is the identification of the "amine toxins" responsible for the symptomatology of hepatic coma, and the reproduction of coma-like states in normal animals by their administration. The significance of these studies lies in the more intelligent management of some of the complications of hepatocellular failure.